Physical exercise is accompanied by increased plasma levels of ammonia but it is not known whether this rise primarily reflects accelerated formation in muscle or decreased removal by the liver. Consequently, leg and splanchnic exchange of ammonia was examined, using the catheter technique, in 11 healthy subjects at rest, during three consecutive 15 min periods of bicycle exercise at gradually increasing work loads (35%, 55% and 80% of maximum oxygen uptake) and for 60 min during post-exercise recovery. The basal arterial ammonia level was 22 +/- 2 mumol/l, the concentration rose curvilinearly in response to increasing work loads (peak value 84 +/- 12 mumol/l), and fell rapidly after exercise, reaching basal levels after 30-60 min. A linear regression was found for ammonia levels in relation to lactate concentrations at rest and during exercise (r = 0.85, P less than 0.001). A significant relationship was also observed between arterial ammonia and alanine levels (r = 0.75, P less than 0.001). Leg tissues showed a net uptake of ammonia in the basal state (2.4 +/- 0.5 mumol/min). During exercise this changed to a net production, which increased curvilinearly with rising work intensity (peak value 46 +/- 15 mumol/min) but reverted to a net ammonia uptake at 30-60 min after exercise. Splanchnic ammonia uptake (basal 12 +/- 2 mumol/min) did not change in response to exercise but increased transiently during the early post-exercise period. From the above observations we conclude that the hyperammonaemia of exercise comes primarily from muscle release, while the splanchnic removal of ammonia is essentially unaltered. Part of the ammonia formed in contracting muscle is most likely used in the synthesis of amino acids, mainly glutamine and probably alanine.